Articles: hyperalgesia.
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Activation of nucleus factor-kappaB (NF-κB) in the dorsal root ganglia (DRG) is critical for development of neuropathic pain. The underlying mechanisms, however, are largely unknown. In the present work we tested if the activation of NF-κB is required for re-expression of Nav1.3, which is important for development of neuropathic pain, in uninjured DRG neurons. ⋯ As our previous work has shown that up-regulation of tumor necrosis factor-alpha (TNF-α) in DRG is responsible for the re-expression of Nav1.3 in uninjured DRG neurons following L5 ventral root injury, we investigated whether activation of NF-κB is essential for the up-regulation of Nav1.3 by TNF-α. Results showed that application of rat recombinant TNF-α (rrTNF) into the cultured normal adult rat DRG neurons increased the immunoreactive (IR) of Nav1.3 localized mainly around the cell membrane and pre-treatment with PDTC blocked the change dose-dependently. The data suggested that injury to ventral root might lead to neuropathic pain and the re-expression of Nav1.3 in primary sensory neurons by activation of NF-κB.
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Physiology & behavior · Dec 2010
Progesterone rapidly recruits female-typical opioid-induced hyperalgesic mechanisms.
Continuous morphine treatment can paradoxically increase nociception (i.e. hyperalgesia) in male and female mice, but sex differences have been reported. Here, we studied progesterone modulation of these differences by assessing nociception on the tail-withdrawal test in male and female mice rendered hyperalgesic during continuous infusion of two different morphine doses (1.6 and 40.0mg/kg/24h). Although the lower morphine infusion dose increased nociception in both sexes by infusion Day 4, this hyperalgesia dissipated by Day 6 in males and ovariectomized females, but not gonadally intact females. ⋯ However, the NMDA receptor antagonist MK-801 (0.05mg/kg) reversed hyperalgesia in males and ovariectomized females but not gonadally intact females on infusion Day 6. Subcutaneous progesterone (0.0016mg/kg) injection inhibited this reversal in male and ovariectomized female mice but had no effect on nociception in saline-infused mice of either sex. These data confirm our previous findings that male and female mice utilize distinct hyperalgesic mechanisms, and show for the first time that a single progesterone bolus dose can recruit female-typical hyperalgesia in ovariectomized females and males.
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Randomized Controlled Trial
A pharmacokinetic and pharmacodynamic study of oral oxycodone in a human experimental pain model of hyperalgesia.
Oxycodone is not as well characterized, with respect to its pharmacokinetic/pharmacodynamic properties, as other opioids. Moreover, the pharmacodynamic profile of oxycodone can be affected by changes in the pain system, e.g. hyperalgesia. Therefore, the aim of this study was to investigate the pharmacokinetic/pharmacodynamic profiles of oxycodone in a human experimental pain model of hyperalgesia. ⋯ There was a measurable effect of oxycodone, compared with placebo, on all pain measures, and a linear concentration-effect relationship without an effect delay was demonstrated. This could indicate an initial peripheral analgesic effect of oxycodone.
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Fibromyalgia syndrome (FM) is a highly prevalent musculoskeletal disorder that is often accompanied by somatic hyperalgesia (enhanced pain from noxious stimuli). Neural mechanisms of somatic hyperalgesia have been analyzed via quantitative sensory testing of FM patients. ⋯ FM pain is likely to be at least partially maintained by peripheral impulse input from deep tissues. This conclusion is supported by results of several studies showing that injection of local anesthetics into painful muscles normalizes somatic hyperalgesia in FM patients.
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Understanding the actions of opioids now encompasses pronociceptive as well as antinociceptive mechanisms. Opioid-induced hyperalgesia (OIH) refers to increased pain sensitivity due to high-dose or prolonged opioid exposure. It has become more important as patients with pain remain on opioids at higher doses for longer periods of time. One setting that highlights the dilemma of OIH is in the opioid-tolerant patient who is hospitalized for painful medical conditions or procedures and is unable to achieve adequate analgesia despite escalating opioid doses. This patient population often requires agents that act synergistically with opioids through different mechanisms to achieve analgesia. Dexmedetomidine is an alpha-2 adrenergic agonist that has been shown to synergize with opioids. ⋯ The cases presented provide support for the clinical utility of alpha-2 agonists during opioid dose reduction in patients with OIH as well suggesting that they may contribute to the recovery of normal nociceptive and antinociceptive responses.